<p>The aims of this work were to image and analyze the needle behavior at automated core biopsy, to investigate the clinical utility of an alternative core biopsy technique using a semiautomated gun in breast and axillary lesions, and also to compare core biopsy with surgical specimens in malignant breast lesions regarding histologic features and hormone receptor expression.</p><p>In two experimental studies, using butter and silicon phantoms, respectively, the needle pass was imaged and its dynamic behavior studied. It was shown that the needle took a curved course in phantoms. It deviated to the same side as where the tip lay, and the degree of the curvature increased with increasing hardness of the phantoms. Our experimental methods can be applied for imaging of needle behavior and thereby improvement of needle configuration.</p><p>In two clinical studies, a semiautomated gun was used for large needle core biopsy of breast and axillary lesions in two series of 145 and 21 patients, respectively. The sensitivity of the method for diagnosis of malignancy was 87% (108/124), and in 37% (31/83) of cases the full length of the needle notch was filled with specimen. No injury to the neurovascular structures of the axillary area was observed. It was concluded that the semiautomated gun can be used as an alternative to the automated gun when the size and location of the lesion render use of the automatic device uncertain or dangerous, e.g., in small breast lesions or lesions located in the axilla.</p><p>In a series of 129 cases of breast cancer, comparison of core biopsy and surgical specimens showed that core biopsy provided enough information on the histologic type and grade of the lesions. Also, there was moderate to high concordance between the two methods for assessment of progesterone receptors and estrogen receptors (Spearman`s kappa 0.67 and 0.89, respectively).</p>

A quantitative evaluation of single photon emission computed tomography (SPECT) and planar scintigraphic imaging may be valuable for both diagnostic and therapeutic purposes. For an accurate quantification it is usually necessary to correct for attenuation and scatter and in some cases also for septal penetration. For planar imaging a background correction for the contribution from over- and underlying tissues is needed. In this work a few correction methods have been evaluated and further developed. Much of the work relies on the Monte Carlo method as a tool for evaluation and optimisation. A method for quantifying the activity of I-125 labelled antibodies in a tumour inoculated in the flank of a mouse, based on planar scintigraphic imaging with a pin-hole collimator, has been developed and two different methods for background subtraction have been compared. The activity estimates of the tumours were compared with measurements in vitro. The major part of this work is attributed to SPECT. A method for attenuation and scatter correction of brain SPECT based on computed tomography (CT) images of the same patient has been developed, using an attenuation map calculated from the CT image volume. The attenuation map is utilised not only for attenuation correction, but also for scatter correction with transmission dependent convolution subtraction (TDCS). A registration method based on fiducial markers, placed on three chosen points during the SPECT examination, was evaluated. The scatter correction method, TDCS, was then optimised for regional cerebral blood flow (rCBF) SPECT with Tc-99m, and was also compared with a related method, convolution scatter subtraction (CSS). TDCS has been claimed to be an iterative technique. This requires however some modifications of the method, which have been demonstrated and evaluated for a simulation with a point source. When the Monte Carlo method is used for evaluation of corrections for septal penetration, it is important that interactions in the collimator are taken into account. A new version of the Monte Carlo program SIMIND with this capability has been evaluated by comparing measured and simulated images and energy spectra. This code was later used for the evaluation of a few different methods for correction of scatter and septal penetration of I-123 brain SPECT. The methods were CSS, TDCS and a method where correction for scatter and septal penetration are included in the iterative reconstruction. This study shows that quantitative accuracy in I-123 brain SPECT benefits from separate modelling of scatter and septal penetration.

The aims of this work were to image and analyze the needle behavior at automated core biopsy, to investigate the clinical utility of an alternative core biopsy technique using a semiautomated gun in breast and axillary lesions, and also to compare core biopsy with surgical specimens in malignant breast lesions regarding histologic features and hormone receptor expression. In two experimental studies, using butter and silicon phantoms, respectively, the needle pass was imaged and its dynamic behavior studied. It was shown that the needle took a curved course in phantoms. It deviated to the same side as where the tip lay, and the degree of the curvature increased with increasing hardness of the phantoms. Our experimental methods can be applied for imaging of needle behavior and thereby improvement of needle configuration. In two clinical studies, a semiautomated gun was used for large needle core biopsy of breast and axillary lesions in two series of 145 and 21 patients, respectively. The sensitivity of the method for diagnosis of malignancy was 87% (108/124), and in 37% (31/83) of cases the full length of the needle notch was filled with specimen. No injury to the neurovascular structures of the axillary area was observed. It was concluded that the semiautomated gun can be used as an alternative to the automated gun when the size and location of the lesion render use of the automatic device uncertain or dangerous, e.g., in small breast lesions or lesions located in the axilla. In a series of 129 cases of breast cancer, comparison of core biopsy and surgical specimens showed that core biopsy provided enough information on the histologic type and grade of the lesions. Also, there was moderate to high concordance between the two methods for assessment of progesterone receptors and estrogen receptors (Spearman`s kappa 0.67 and 0.89, respectively).

Developing radiation delivery systems for optimisation of absorbed dose to the target without normal tissue toxicity requires advanced calculations for transport of radiation. In this thesis absorbed dose and fluence in different radiotherapy applications were calculated by using Monte Carlo (MC) simulations. In paper I-III external neutron activation of gadolinium (Gd) for intravascular brachytherapy (GdNCB) and tumour therapy (GdNCT) was investigated. MC codes MCNP and GEANT4 were compared. MCNP was chosen for neutron capture reaction calculations. Gd neutron capture reaction includes both very short range (Auger electrons) and long range (IC electrons and gamma) products. In GdNCB the high-energetic gamma gives an almost flat absorbed dose delivery pattern, up to 4 mm around the stent. Dose distribution at the edges and inside the stent may prevent stent edge and in-stent restenosis. For GdNCT the absorbed dose from prompt gamma will dominate over the dose from IC and Auger electrons in an in vivo situation. The absorbed dose from IC electrons will enhance the total absorbed dose in the tumours and contribute to the cell killing. In paper IV a model for calculation of inter-cluster cross-fire radiation dose from β-emitting radionuclides in a breast cancer model was developed. GEANT4 was used for obtaining absorbed dose. The dose internally in cells binding the isotope (self-dose) increased with decreasing β-energy except for the radionuclides with substantial amounts of conversion electrons and Auger electrons. An effective therapy approach may be a combination of radionuclides where the high self-dose from nuclides with low β-energy should be combined with the inter-cell cluster cross-fire dose from high energy β-particles. In paper V MC simulations using correlated sampling together with importance sampling were used to calculate spectra perturbations in detector volumes caused by the detector silicon chip and its encapsulation. Penelope and EGSnrc were used and yielded similar results. The low energy part of the electron spectrum increased but to a less extent if the silicon detector was encapsulated in low z-materials.

To diagnose rheumatoid arthritis (RA) during the early stages of the disease is often difficult. The disease course shows great inter-individual variation from mild, self-limiting to very severe destruc-tive disease with extra-articular manifestations. Early aggressive treatment with potentially toxic drugs has been shown to improve the long-term outcome. Thus, it is desirable to make an early reliable di-agnosis and to identify those patients who would benefit from being treated most aggressively. The aim of this thesis was to evaluate laboratory and clinically markers of inflammation as predic-tors of disease course, to compare dual-energy X-ray absorptiometry (DXA) and conventional radiog-raphy (CR) as measures of joint destruction and to investigate the significance of antibodies against cyclic citrullinated peptide (anti-CCP antibodies), rheumatoid factors (RFs) and HLA shared epitope (SE) alleles for the relative risk of future development of RA and as predictors of disease severity in patients with early RA. Patients with RA of recent onset are included in the early RA programme at the Department of Rheumatology, University Hospital, Umeå and are followed longitudinally. The prediction of markers of inflammation for bone loss and radiological outcome was analyzed in the first 43 patients recruited. Radiographs of hands and feet (Larsen score) and bone mineral density (BMD) in hands (DXA), were assessed at baseline, after 1 and 2 years. The disease activity was evaluated clinically and by labora-tory tests. Radiological damage increased significantly during the study and was particularly corre-lated with Larsen score at baseline. BMD in hands decreased significantly in postmenopausal women and the decrease was greater than in healthy matched controls. Radiological progression and bone loss in hands was retarded by an early response to therapy. In a case-control study within the Medical Biobank and the Maternity cohort of Northern Sweden, patients from the early RA programme were identified among blood donors from whom samples had been collected years before onset of symptoms. The prevalence of anti-CCP antibodies and RFs (IgA-RF, IgG-RF and IgM-RF) was investigated in samples from 83 individuals (pre-patients) and com-pared with matched controls. SE alleles were assessed in a sub-group of 59 individuals. Anti-CCP antibodies and RFs preceded onset of RA by several years and increased in prevalence closer to dis-ease onset. Anti-CCP antibodies and IgA-RF significantly predicted the onset of RA. The combination of anti-CCP antibodies and SE alleles was associated with a high relative risk for future development of RA. In a later co-analysis between the register of patients in the early RA programme (n=138) and the Medical Biobank and the Maternity cohort, 93 pre-patient samples were identified. The significance of SE alleles and of the presence of anti-CCP antibodies and RFs before and at disease onset for disease activity and severity was studied. Radiographs of hands and feet were assessed at baseline and after 2 years (Larsen score). The presence of anti-CCP antibodies in pre-patient samples and at baseline was associated with radiological damage, as was presence of all RFs at baseline. A higher titre of anti-CCP antibodies was associated with greater radiological progression. The titre was lowered by a therapeutic response. In multiple logistic regression analyses anti-CCP antibodies, IgA-RF, ESR and swollen joint count predicted greater radiological progression, whilst a therapeutic response predicted a lesser pro-gression. In conclusion, anti-CCP antibodies and IgA-RF are predictors for future onset of RA and for radio-logical destruction and progression. The combination of anti-CCP antibodies and SE alleles is associ-ated with a high relative risk for future RA. Therapeutic response decreases the radiological progres-sion and the bone loss in hands and lowers the titre of anti-CCP antibodies. Conventional radiography is a better measure of joint destruction than DXA.

Se estudian 7.176 informes oficiales de control de calidad de instalaciones de radiodiagnóstico dental pertenecientes a clínicas odontológicas que utilizan algún tipo de aparato de radiología intraoral. El estudio evolutivo corresponde a las cinco primeras revisiones de dichas instalaciones como consecuencia de la nueva normativa en la que se establecen las obligaciones que deben cumplir este tipo de instalaciones (1997-2001). Los resultados exponen un análisis cuantitativo de los parámetros, recogidos en dichos informes, con especial referencia a las características fIsicas (kVp, mA. filtración, colimador, longitud del disparador), así como las desviaciones detectadas en su funcionamiento. Se determinan las características del proceso de obtención de las imágenes radiológicas en dichas instalaciones (tipo revelado, control de tiempos de revelado, renovación de líquidos, tipo película radiogrifica, almacenamiento y caducidad de la película) y la dosis media de radiación ionizante empleada en las mismas para obtener la imagen radiológica de una misma pieza dental en las condiciones de trabajo habituales en cada una de las salas. Todo ello en su proceso evolutivo durante los cinco años posteriores a la instauración de la normativa de control de calidad. En general, los resultados obtenidos muestran una disminución del 18.75 % en las dosis medias administradas durante estos cinco años de estudio. El 97.98 % de las instalaciones radiológícas dentales estudiadas emplean dosis iguales o inferiores a 7 mGy para la realización de la exploración analizada y que corresponde a la dosis máxima de referencia recomendada en radiología intraoral. Sin embargo, sólo el 72.79% de las instalaciones radiológícas podrían llegar a cumplir todas las recomendaciones de la Unión Europea sobre las características de funcionamiento de estos equipos. Aunque el grado de cumplimiento de las recomendaciones oficiales sobre protección radiológíca no es satisfactoria. se han observado mejorías significativas en la actuación radiológíca dental por parte del profesional a lo largo de estos cinco años de evolución. Por ello, la instauración de la normativa legal esta produciendo una mejoría lenta pero progresiva de la actuación dental en España. / ' A total of 7.176 official reports on dental surgeries of cIinics in Spain are analysed. Tbe study covered the period 1997 to 2001 as consecuence of the entry into force of a new Royal Decree and dental surgeries have to undergo an annual control of quality. Tbe results shows a quantitative análisis of the variables studied in the ~ oficial reports, particu1ar1y physical characteristics of the X-ray equipments (kVp, mA, filtration thickness, collimator, lenth of tube), besides anomalies in their correct way of working. Processing of film characteristics (type of processing, control in processing time, renewal of liquids, type of film, storage and film expiration) and mean dose of ionizaing radiation are determined in habitual conditions. This study have been carried out during the 5 years following the introducction of the EU norm concerning radiological quality control .In general. the mean dose received by patients fell during the 5 years studied by 18.75 %. Meanwhile, the 97.98 % of equipments fulfil1ed the EU recommendation and did not excede 7 mGy on average per shot. However, only the 72.79 % of dental radiological equipments could follow the UE recommendations on a correct way of working. Although EU recommendations concerning radiological protection in dental clinics are not met in all cases, it have been detected significant improvements in professional behaviour during this five years of study. The establishment of the new legislation has led a gradual improvement in Spanish dental radiology practices.

A random search optimization method based off an analogous process for the slow cooling of metals is explored and used to find the optimum solution for a number of regression models that analyze nuclear, radiological, biological,and chemical terrorism targets. A non-parametric simulation based off of historical data is also explored. Simulated series of 30 years and a 30 year extrapolation of historical data are provided. The inclusion of independent variables used in the regression analysis is based off existing work in the reviewed literature. CBRN terrorism data is collected from both the Monterey Institute's Weapons of Mass Destruction Terrorism Database as well as from the START Global Terrorism Database. Building similar models to those found in the literature and running them against CBRN terrorism incidence data determines if conventional terrorism indicator variables are also significant predictors of CBRN terrorism targets. The negative binomial model was determined to be the best regression model available for the data analysis. Two general types of models are developed, including an economic development model and a political risk model. From the economic development model we find that national GDP, GDP per capita, trade openness, and democracy to significant indicators of CBRN terrorism targets. Additionally from the political risk model we find corrupt, stable, and democratic regimes more likely to experience a CBRN event. We do not find language/religious fractionalization to be a significant predictive variable. Similarly we do not find ethnic tensions, involvement in external conflict, or a military government to have significant predictive value.

This research investigates the use of G-M counters to triage the individuals who have been exposed to a Radiological Dispersal Device (RDD). Upon being exposed to an RDD, inhalation of the airborne radionuclide is a method which someone can receive a considerable amount of dose. Bioassay via analysis of excreta is a commonly used method of determining the dose received, yet it would be cumbersome if there are a large number of people needing to be screened. An in vivo method must be considered so that a non-intrusive and more efficient triaging method can be implemented. Whole body counters are commonly used in counting facilities as an in vivo bioassay method, yet they are limited in number and not easily portable. Therefore, a more portable and more common detection device should be considered. G-M survey meters are common devices that are highly portable, making them ideal candidates to fulfill this necessity. The ease of use contributes to the viability of the device as a portable, in vivo screening device. To analyze this detector, a Monte Carlo model of the detector was created to be used in simulations with the Medical Internal Radiation Dose phantoms. The detector was placed in a few locations on the phantoms. Four locations were strategically chosen for detector placement: the posterior upper right torso, the anterior upper right torso, the lateral upper thigh, and the anterior of the neck. Six phantoms were considered: Reference Male, Female, Adipose Male, Adipose Female, Post Menopausal Adipose Female, and a Child. Six radionuclides were investigated: Am-241, Co-60, Cs-137, I-131, Ir-192, and Sr-90. The nuclides were distributed throughout the phantoms according to Dose and Risk Calculation Software, a code that determines how a radionuclide is distributed over time upon inhalation, ingestion, or injection. A set of time dependent guidelines were developed, determining the count rate per unit dose inhaled for each detector location and phantom type.

Ce travail de thèse introduit une nouvelle méthode pour la caractérisation radiologique des déchets très faiblement radioactifs produits au sein de l’Organisation Européenne pour la Recherche Nucléaire (CERN). La méthode se base sur : 1. le calcul des radionucléides en présence, i.e. les radionucléides qui peuvent être produits lors de l’interaction des particules avec la matière et les structures environnantes les accélérateurs, 2. la mesure directe des émetteurs gamma et, 3. la quantification des émetteurs alpha et beta purs et de rayons X de faible énergie, appelés radionucléides difficile-a-mesurer (DTM), en utilisant les méthodes dites des «scaling factor» (SF), «correlation factor» (CF) et activité moyenne (MA). La première phase du processus de caractérisation est le calcul des radionucléides en présence à l’aide de codes de calcul analytiques ou Monte Carlo. Après le calcul de l’inventaire radiologique, les radionucléides émetteurs gamma sont mesurés par spectrométrie gamma dans chaque colis de la population. L’émetteur gamma dominant, appelé « key nuclide » (KN), est identifié. La méthode dite des «scaling factors» permet d’estimer l’activité des radionucléides DTM après évaluation de la corrélation entre l’activité des DTM et l’activité de l’émetteur gamma dominant obtenue à partir d’échantillons. Si une corrélation existe, l’activité des radionucléides DTM peut être évaluée grâce à des facteurs de corrélation expérimentaux appelés « scaling factors », sinon l’activité moyenne obtenue à partir d’échantillons prélevés dans la population est attribuée à chaque colis. Lorsque les activités des émetteurs alpha et beta purs et des émetteurs X de faible énergie ne peuvent pas être estimées par mesure la méthode des « correlation factors » s’applique. La méthode des « correlation factors » se base sur le calcul de corrélations théoriques entre l’émetteur gamma dominant et les radionucléides de très faible activité. Cette thèse décrit en détail la nouvelle technique de caractérisation radiologique, montre un cas d’application complet et présente les résultats de l’industrialisation de la méthode ayant permis la caractérisation radiologique de plus de 1000 m3 de déchets radioactifs au CERN entre 2015 et 2017. / This thesis introduces a new method to characterize metallic very-low-level radioactive waste produced at the European Organization for Nuclear Research (CERN). The method is based on: 1. the calculation of a preliminary radionuclide inventory, which is the list of the radionuclides that can be produced when particles interact with a surrounding medium, 2. the direct measurement of gamma emitters and, 3. the quantification of pure-alpha, pure-beta and low-energy X-ray emitters, called difficult-to-measure (DTM) radionuclides, using the so-called scaling factor (SF), correlation factor (CF) and mean activity (MA) techniques. The first stage of the characterization process is the calculation of the radionuclide inventory via either analytical or Monte Carlo codes. Once the preliminary radionuclide inventory is obtained, the gamma-emitting radionuclides are measured via gamma-ray spectrometry on each package of the waste population. The major gamma-emitter, called key nuclide (KN), is also identified. The scaling factor method estimates the activity of DTM radionuclides by checking for a consistent and repeated relationship between the key nuclide and the activity of the difficult to measure radionuclides from samples. If a correlation exists the activity of DTM radiodionuclides can be evaluated using the scaling factor otherwise the mean activity from the samples collected is applied to the entire waste population. Finally, the correlation factor is used when the activity of pure-alpha, pure-beta and low-energy X-ray emitters is so low that cannot be quantified using experimental values. In this case a theoretical correlation factor is obtained from the calculations to link the activity of the radionuclides we want to quantify and the activity of the key nuclide. The thesis describes in detail the characterization method, shows a complete case study and describes the industrial-scale application of the characterization method on over 1’000 m3 of radioactive waste, which was carried out at CERN between 2015 and 2017.

Em medicina nuclear, os trabalhadores diretamente envolvidos nos exames são frequentemente expostos à radiação ionizante. Neste estudo, utilizou-se um detector Geiger-Mueller (GM) para medir as doses da radiação ocupacional durante a realização de algumas das etapas mais críticas para a exposição à radiação em exames de cintilografia de perfusão miocárdica (CPM), são elas: 1) fracionamento das atividades no preparo das seringas; 2) administração do radiofármaco Tecnécio99m-sestamibi nas etapas de repouso e estresse; e 3) aquisição das imagens diagnósticas na sala de exames. Na avaliação, procurou-se discriminar e relacionar o tempo de experiência profissional às doses medidas. Para isso, foi acompanhado um total de 494 procedimentos entre os meses de outubro e dezembro de 2012, sendo 229 seringas preparadas no fracionamento das atividades, 165 administrações de radiofármaco (55 na etapa de repouso realizadas por profissionais com tempo de experiência superior a 2 anos, 55 na etapa de repouso realizada por profissionais com tempo de experiência inferior a 1 ano, e 55 na etapa de estresse), e 100 aquisições de imagem (50 na etapa de repouso e 50 na etapa de estresse). Foram avaliados também os registros das doses obtidas na monitoração individual por dosimetria termoluminescente (TLD), realizada entre julho de 2010 e dezembro de 2012. Os resultados obtidos com o detector GM, quando extrapolados para o acúmulo de doses no período de um ano, mostraram-se significantes em relação ao limite anual de 20 mSv determinado pela legislação brasileira para uma média em cinco anos consecutivos. As doses médias acumuladas nos procedimentos avaliados corresponderam aos seguintes percentuais em relação a esse limite: 1) 13%, no fracionamento das atividades; 2) 8% e 35%, na administração dos radiofármacos das etapas de repouso e estresse, respectivamente; e 3) 4% e 10%, na aquisição das imagens das etapas de repouso e estresse, respectivamente. Esses valores foram compatíveis com os resultados da monitoração individual por TLD, cujos valores registrados foram superiores (34,6% a 63,2% do limite de 20 mSv) pelo fato de não discriminar as doses em cada procedimento. Em virtude dos valores de dose encontrados, o uso de equipamentos de proteção individual e a agilidade na realização dos procedimentos, ligada a experiência profissional, contribuem de forma efetiva para a redução destes valores de dose. / In nuclear medicine, workers directly involved in the exams are frequently exposed to ionizing radiation. In this study, a Geiger-Mueller detector was used to measure the occupational radiation doses while conducting some of the steps with critical radiation exposure during myocardial perfusion scintigraphy exams, which are: 1) fractionation of radiopharmaceutical activities in single-dose syringes, 2) Technetium99m-sestamibi administration during rest and stress steps, and 3) diagnostic images acquisition in the exam room. In the evaluation, it was sought to distinguish and relate the length of professional experience to measured doses. For that reason a total of 494 procedures were followed up including 229 fractionation of radiopharmaceutical activities in single-dose syringes, 165 radiopharmaceutical administrations (55 during rest step performed by professionals with experience time above two years, 55 during rest step performed by professionals with experience time below one year, and 55 during stress step), and 100 image acquisitions (50 during rest step and 50 during stress step). Dose records obtained during individual monitoring by thermoluminescent dosimetry (TLD) conducted between July 2010 and December 2012 were also evaluated. The results obtained by the GM detector, when extrapolated for dose accumulation over one year, proved to be significant in relation to the 20 mSv annual limit determined by Brazilian regulations to an average over five consecutive years. The mean accumulated doses evaluated during the procedures correspond to the following percentages relative to the annual limit value: 1) 13%, at the fractionation of radiopharmaceutical activities, 2) 8% and 35%, during rest and stress steps of radiopharmaceuticals administration, respectively, and 3) 4% and 10%, during rest and stress images acquisition, respectively. These values are consistent to the results of individual monitoring by TLD. These values were consistent to the results of individual monitoring by TLD, whose registered values were higher (34.6% to 63.2% of the limit of 20 mSv) due to the fact that they don't discriminate the dose by each procedure. Because of the dose values found, the use of personal protective equipment and the agility in procedures, linked to professional experience, effectively contribute to the reduction of these dose values.